Background: Vulvovaginal atrophy (VVA) significantly impacts the quality of life in breast cancer patients leading to symptoms like vaginal dryness, dyspareunia, and genital discomfort. Quality of life in this context is measured using validated scales like the Vaginal Health Index, Visual Analog Scale (VAS), and the Female Sexual Function Index (FSFI). Methods: We performed a systematic review and meta-analysis to identify effective treatment options for VVA, including topical estrogen, systemic hormone therapy, vaginal DHEA, ospemifene, and non-hormonal methods like intravaginal laser therapy, moisturizers, and lubricants. A systematic search of four databases (MEDLINE, Scopus, CENTRAL, Embase) identified studies on VVA treatment efficacy in breast cancer patients, yielding 13,039 records, with 32 eligible studies and 8 included in the meta-analysis. Results: Significant improvements were found with intravaginal laser therapy, showing notable differences in the Vaginal Health Index (MD = 8.24, p < 0.01), dyspareunia (MD = −4.82, p = 0.05), and dryness (MD = −5.05, p = 0.01). However, no significant changes were observed in FSFI and vaginal pH. Notably only intravaginal laser therapy was included in the meta-analysis, as other treatment options lacked comparable data. Both hormonal and non-hormonal treatments improved quality of life, with laser therapy showing the most substantial effects. Conclusions: Intravaginal laser therapy is an effective treatment for VVA symptoms in breast cancer survivors, particularly in improving the Vaginal Health Index and reducing dyspareunia. Despite the strengths of the study, variability among studies, lack of RCT-s and data limitations, especially on long-term effects, present challenges.

Background: Delivering contraceptive hormones through a transdermal patch or a vaginal ring might have advantages over the traditional oral route. Objectives: To compare the effectiveness, compliance, and side effect profile of oral and parenteral drug administration methods. Methods: We performed a systematic literature search in four medical databases—MEDLINE (via PubMed), Cochrane Library (CENTRAL), Embase, and Scopus—from inception to 20 November 2022. Randomized controlled trials assessing the efficacy, compliance, and adverse event profile of combined parenteral and oral hormonal contraceptives were included. Results: Our systematic search provided 3952 records; after duplicate removal, we screened 2707 duplicate-free records. A total of 13 eligible studies were identified after title, abstract, and full-text selection. We observed no significant difference in contraceptive efficacy (Pearl Index) between oral and parenteral drug administration (MD = −0.06, CI: −0.66–0.53; I² = 0%). We found significant subgroup differences between parenteral methods in terms of compliance (χ² = 4.32, p =0.038, I² = 80%) and certain adverse events: breast discomfort (χ² = 19.04, p =0.001, I² = 80%), nausea (χ² = 8.04, p =0.005, I² = 75%), and vomiting (χ² = 9.30, p =0.002; I² = 72%). Conclusion: Both parenteral and oral contraceptives can be used as an effective contraceptive method, and the route of administration should be tailored to patient needs and adverse event occurrence.

Introduction: Optimal systemic treatment for recurrent or advanced endometrial cancer (EC) remains uncertain, particularly in the second-line setting. While first-line chemotherapy with paclitaxel and carboplatin is widely used, its efficacy is limited. Recent evidence suggests that adding immune checkpoint inhibitors (ICIs) to chemotherapy (ChT) can improve progression-free survival (PFS). In addition, hormonal therapies (such as progestins and aromatase inhibitors), targeted therapies and ICIs used alone or in combination are emerging as potential treatment options. Objectives: Our objective was to systematically evaluate the efficacy and safety of systemic therapies beyond standard ChT for patients with recurrent or advanced EC, focusing on progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs), prospective studies, and retrospective studies up to June 2024 on PubMed, Embase, and CENTRAL. Studies evaluating systemic therapies—chemotherapy, hormonal therapy, targeted agents, and ICIs—in recurrent or advanced EC were included. Primary outcomes were PFS and OS; secondary outcomes included grade ≥ 3 treatment-related adverse events. Risk of bias was assessed using the Cochrane RoB 2 and MINORS tools, and GRADE was applied to evaluate the certainty of evidence. Results: Five RCTs evaluated the addition of ICI to conventional ChT. In mismatch repair-deficient (MMRd) patients, the addition of ICI significantly improved PFS and OS compared to the ChT-only group. In mismatch repair-deficient (MMRd) patients, the median PFS (mPFS) was 8.39 months in the ChT group and 22.73 months in the ICI group (HR: 0.34, p < 0.001). OS results were 26.48 and 41.36 months, respectively. In mismatch repair-proficient (MMRp) patients, mPFS was 9.4 months in the ChT group and 10.18 months at the ICI group (HR: 0.72, p = 0.002). OS was 27.37 and 27.79 months, respectively. We conducted several exploratory single-arm subgroup analyses and multiple individual patient data (IPD) meta-analyses across several clinically relevant subgroups, including patients treated with progestins, lenvatinib plus pembrolizumab, PI3K/AKT/mTOR inhibitor monotherapy, and PI3K/AKT/mTOR inhibitors in combination with aromatase inhibitors. Detailed descriptive analyses were performed for each subgroup. Conclusions: Combining chemotherapy with ICIs appears to show the most favorable survival outcomes, especially in MMRd tumors. Taking into account the methodological limitations inherent in the elaboration of lower-level evidence and IPD, hormonal and targeted therapies might be considered viable options, with efficacy and safety profiles dependent on tumor biology. Better stratification of the EC patient cohort is warranted.